ItemThe Effect of Vascularization and Tissue Type on Cryosurgical ProceduresMagleby, Reed; Schallop, Amanda; Shulman, Eric; Sterling, Joshua (2008-07-23T20:42:01Z)Cryosurgery is a minimally-invasive surgical procedure that is used in the treatment of multiple types of cancer. Although cryosurgical treatments, which involve the application of extreme cold to diseased or cancerous tissue, are often used in the treatment of near-surface skin cancer, they have also been used to treat several other types of internal cancers, including those in the prostate, liver, and kidney. Although fundamentally similar, many of these tissues differ significantly in properties such as density, vascularization, and thermal conductivity. A major issue in cryosurgery is adapting the procedure to different tissue types. In this study, the effect of tissue perfusivity on the outcomes of cryosurgery was modeled using the COMSOL software. For the purposes of comparison, the properties of lung tissue, which is highly perfused and not as conductive, and liver tissue, which is mildly perfused and more conductive, were used. The procedure was modeled as a 10 mm diameter cryoprobe set at a temperature of -196?C in a cylindrical region of tissue 8 cm in height and 8 cm in diameter. The time required for a 26mm diameter spherical tumor to reach -45?C was determined in four scenarios, lung tissue and liver tissue both with and without blood perfusion. Although metabolic heat generation was also included, sensitivity analysis showed it to be a minor factor in the cooling process. Results showed blood perfusivity to have a significant effect on freezing time in lung tissue and a relatively minor one in liver tissue: although the addition of perfusion caused freezing time in the liver to increase from 200 to 250 seconds, the addition of perfusion in the lung tissue caused the freezing front to never reach the tumor edge. Sensitivity analyses also revealed the freezing process to be highly sensitive to conductivity as well. It was therefore concluded that although blood perfusion is one of the most important heat transfer processes in cryosurgery, tissue conductivity is just as, if not more important. We recommend that cryosurgery continue to be used as a treatment for liver tumors, but further studies are needed to determine its efficacy in highly perfused, porous tissue such as the lung. ItemComparison of Oxygen Flux in Hydrogel and Silicone Hydrogel Contact LensesCohan, Jonathan; Cho, Eun Ae; Connors, Megan (2008-07-23T20:35:52Z)The prevalence of contact lens use has been continuously growing for their convenience and for cosmetic reasons. Although contact lenses do offer many advantages over glasses, the major concern for many contact lens users is dryness that results from a lack of oxygen that goes through the contact lens to meet the demand of eye tissue. A new type of contact lens, made out of silicone hydrogel, has been introduced in the market which has garnered much attention from many contact users. The silicone hydrogel is different from the traditional hydrogel contact lens since oxygen is permeable through silicone, which was not possible through hydrogels. The hydrogel contact lenses must have high water content for oxygen delivery, silicone hydrogel contacts depends on their high oxygen diffusivity while having low water content. Night and day contact lenses are made out of silicone hydrogel whereas traditional ones for day use are often made out of hydrogel. A model was developed to validate the advantage of wearing silicone hydrogel contact lenses in both day and night conditions. By analyzing the center area of the eye around the pupil as a thin slab, the performance of these two types of contact lenses were compared by computing average oxygen concentrations in the stroma, which is the largest layer of cornea. Using COMSOL Multiphysics, the simplified geometry that included the layers of contact lens, tear, endothelium, and stroma was used as our model to find the oxygen concentration after eight hours of use either with eyes open or closed. The thickness of 80/mu m was used for both hydrogel and silicone hydrogel, the average oxygen concentration was found to be 9.100219x10-8mol/cm3 and 4.198608x10-8 mol/cm3 respectively for day setting with eyes open for eight hours and 3.536442x10-8 mol/cm3 and 2.119774x10-8 mol/cm3 respectively for night setting with eyes closed. Variations of other parameters in modeling also showed the same trend that silicone hydrogel contact lenses ended up with less oxygen in the cornea than hydrogel. Thus, the modeling showed how the silicone hydrogel did not offer any increase in oxygen delivery in both day and night settings. ItemModeling and Optimization of a Bioartificial Implant to Alleviate DiabetesHung, Ben; Fe, Alex; Schmidt, Greg (2008-07-23T20:26:38Z)Diabetes is a chronic disease that is characterized by a person having too high blood sugar levels due to the deficiency of insulin. If left untreated, there is serious risk for development of cardiovascular diseases, renal failure, blindness, nerve damage, etc. Currently, this condition is treated by constant monitoring combined with insulin injection. Given that the various forms of this treatment have negative effects on overall quality of life, this paper focuses on modeling a different type of treatment that can potentially reduce the need for constant blood monitoring and reduce the need for insulin supplementation. The treatment involves surgically implanting a shunt with Beta-islet cells next to a blood vessel in the body . Here, the Beta-islet cells release insulin that follows a bell-shaped curve when graphed vs. time , and this insulin diffuses across a semi-permeable membrane and into the bloodstream. After analyzing the results of the model, it was determined that insulin levels with the implant matched very closely with natural physiological levels, making this treatment a viable one. This treatment also showed the ability to emit a variety of insulin levels making it suitable for a wide variety of patients. This makes this a potentially important avenue of research and worthy of further study. ItemPhotothermolysis Treatment of Acne and the Effects on Healthy Surrounding TissueChin, Karen; Huang, Wilson; Peng, David; Shum, Jennifer (2008-07-23T20:19:22Z)Acne vulgaris, mostly known as pimple, is common among humans in various ages. Many treatments are available to treat acnes. With the current most effective treatment of ace, isotretinoin, having side effects, photothermolysis therapy, a process that uses absorption of light to produce thermal damages, offers a new solution for acne or skin scar removals. Many different types of lasers are available for this photothermolysis procedure. For the simulation of this study, we choose to use the 1450nm laser to model the heat transfer process for the skin layers and the acne region and examine the effects of the whole procedure to the acne region and the surrounding healthy skin tissues. The model of the acne treatment involves a total of five steps of cooling process using low temperature refrigerant and four steps of heating process using the1450nm laser. To simplify the complexity of the skin tissues for this model, we use 2-D axis symmetry for the skin layers, including epidermis, sebaceous glands (acne region), and dermis, and each layer?s thickness is followed as closely as possible to human skin surfaces to make the model more realistic. With the diffusion approximation finite element analysis, we are able to evaluate the temperature profiles in different skin layers and the target acne region and gain insights on the potential acne and healthy skin thermal damages with the 1450nm laser. ItemThink Before You Ink: Modeling Laser Tattoo RemovalCumnock, Katherine; Gerson, Leigh; Stroncek, Jackie; Yagerman, Sarah (2008-07-23T20:04:38Z)Prior to laser treatment tattoos were removed by destroying the skin containing the ink. The skin would be burned, frozen, or excised surgically. The use of Q-Switched lasers has effectively diminished the abrasive nature of tattoo removal with successful results and is now a commonly used method for tattoo removal. Scientific studies have been conducted that examine the laser intensities and mechanism of removal. These studies have found that the laser selectively heats the thin ink layer beneath the skin, leading to an explosion of the microscopic ink particles. The remnants of these particles, and the cells in which they reside, are subsequently removed by the lymphatic system. The primary aim of this project is to model this laser tattoo removal process. This model uses the heat transfer equation with a laser heat generation term to find the temperature profiles of the ink and surrounding skin layers. Also included in the model are the heat energy effects of evaporation within the tissue as it is heated. A mass transfer equation accounts for the moisture content of the tissue as it is lost to vaporization during heating. Sensitivity analyses performed during the modeling process produced optimal values for the absorptivity of the ink for the Q-Switched Ruby laser, 165m-1. They also determined the optimal value for the absorptivity of the skin, 20 m-1. The developed model was validated with clinical experimental results which claimed that within one 40 nanosecond laser pulse time, the ink particles reached 900 degrees Celsius while the surrounding skin temperature was between 45 and 55 degrees Celsius. Further applications of this model include optimizing laser intensities and pulsation times to reduce the tissue damage and the pain of the procedure. ItemTreating Glaucoma with Porous Contact LensAdams, Amie; Glass, Zachary; Schmidt, Gretchen; Xie, Jeanne (2008-07-23T19:58:40Z)Glaucoma is a family of diseases that afflicts 65 million people worldwide. Primary open angle glaucoma is the most common type of glaucoma. This is characterized by increased intraocular pressure (IOP) within the eye that results in vision loss. Current therapeutic drugs include Timolol and Brimonidine which studies have shown to yield a greater decrease in IOP through combined drug therapy than monotherapy. In 2007 Combigan, an eye drop that combines the therapeutic effects of Timolol and Brimonidine, was approved for use by the FDA. This project proposes a method for treating glaucoma through delivery of Combigan via a contact lens through which the drugs will diffuse into the eye over a period of time. We modeled the diffusion of two drugs, Timolol and Brimonidine, through four layers of the human eye. The drug was delivered via a contact lens, so that the concentration of drug in the aqueous humor would remain above the minimum effective dosage for longer than if it were delivered via eye drops. We calculated the concentration of each drug in all layers of the eye for 12 hours. Our model was verified by experimental data in the published literature. Our model failed to deliver solely Timolol or Brimonidine for 12 hours, which was our goal, but still was significantly more effective than eye drops. However, throughout the twelve hours there was at least one drug in the aqueous humor and since both drugs lower IOP through different mechanisms our model did deliver treat the glaucoma for the whole twelve hours. If it were possible to lower the diffusivity of Timolol through the stroma, this would allow for Timolol to remain longer in the aqueous humor thus making the contacts better at treating glaucoma. A sensitivity analysis demonstrated that our model was robust in the tear film and relatively robust in the contact lens. However, the model was particularly sensitive to diffusivity in the stroma layer, as the stroma acts as the final barrier to aqueous humoral penetration and is quite thick. Brimonidine was delivered at a more constant rate, but at a lower concentration than Timolol. It also took six times longer than Timolol to reach its maximum concentration in the aqueous humor. Drug delivery via contact lenses is a feasible technology as more effective than eye drops, but can be improved by designing a time-release drug that diffuses more slowly. Further research needs to be conducted in order to investigate the practicality of this method. ItemDrug Delivery via GLIADEL Wafer for Treatment of Glioblastoma Multiforme (GBM)Ericksen, William Leif; Fortin, Lyndsey; Hou, Cheryl; Shum, Katrina (2008-07-23T19:53:42Z)Glioblastoma multiforme (GBM), one of the most common primary glial tumors, is often treated with tumor resection surgery combined with GLIADEL wafers containing carmustine. These wafers are made with a degradable polymer that releases carmustine over a period of 5 days. Due to the localized nature of the release, no pharmacokinetic measurements have been taken in humans. In order to study the mass transfer of carmustine, COMSOL Multiphysics was used model the process and solve the transient convection-diffusion problem involved. A 2D axisymmetric geometry was used as a simplified schematic involving the wafer, tumor tissue, and normal tissue regions. Input parameters of diffusivity, reaction rates, and velocities were obtained from research involving carmustine drug delivery in human and monkey tissues. Results obtained showed a large initial increase of drug concentration within the first 12 hours localized within the tumor, followed by an exponential decrease during the remaining time period. This shows that the majority of cellular death was within the tumor. Results also indicated that elimination rate, velocity, and diffusivity were sensitive parameters. Furthermore, the model gave insight into what parameters can be changed in order to increase the concentration of carmustine in the tumor and decrease the concentration in the healthy tissue. Carmustine must be delivered to the tumor tissue at a certain concentration to be effective, so optimizing the parameters involved would create a better drug delivery system. ItemModeling Heat-Transfer of the Olympic Cool-Cap System(R)Pathak, Kalpana; Yu, Nansen; Shoffstall, Andrew; Zheng, Laura (2008-07-23T19:37:10Z)Hypoxic-ischemic encephalopathy (HIE), or brain damage due to low blood flow and oxygen deprivation, causes 6 deaths per 1,000 births (Long and Brandon 293). HIE can be caused by cord prolapse, abruptio placentae, maternal hypotension, and asphyxia due to shoulder dystocia, but many times the cause is unknown. The Olympic Cool-Cap system (OCCS) from Natus Medical Inc. was developed to treat HIE in asphyxiated newborn by selectively cooling the brain temperature while maintaining body core temperatures between 34 - 35?C. We modeled this heat-transfer process in the infant head using COMSOL Multiphysics. Our results showed that the gray matter temperature changes by 7oC, while the inner brain temperature remained relatively close to the core temperature. The majority of the cooling occurred at the surface and skull of the head primarily due to the high blood-perfusion of the inner brain. However, the average overall brain temperature still reached 33.45oC, which has been shown in animal studies to be within the therapeutically effective temperature range to treat HIE. Our results suggest that the OCCS has been clinically effective by uniformly cooling the surface of the brain, even though the deep brain remains essentially constant. ItemDesign of Transmucosal Patch for Fentanyl Delivery to Cancer PatientsVan Breugel, Floris; Reznik, Ed; Burnett, Nick; Frid, Simon (2008-07-23T19:24:58Z)Fentanyl is an analgesic that is about 80 times more potent than morphine. It is administered as a transdermal patch for chronic pain relief and as an oral transmucosal lozenge for breakthrough pain relief which is often experienced by cancer patients. The latter administration, under the brand Actiq? exploits the higher permeability of buccal mucosa to achieve a much faster onset. We developed a model of a transmucosal patch as an alternative to existing designs, in order to achieve faster pain relief, improved dosage efficiency, and greater pharmacokinetic control via an impermeable layer. We simplified the design in to 1D model with diffusion and a reaction rate, which simulates uptake fentanyl into the blood. After implementing the model in COMSOL, we calculated the pharmacokinetic profile of fentanyl in the plasma over time with first order linear non homogenous equation. Our resultant profile peaks at 20 minutes and matches Actiq??s profile. A sensitivity analysis yielded that the plasma elimination rate of fentanyl, the epithelium diffusivity and the diffusivity, thickness and distance of the impermeable layer all had a significant affect on the time to peak. A second sensitivity analysis determined that the initial concentration and diffusivity, thickness and distance of the impermeable layer had the greatest influence on peak fentanyl concentration. In conclusion, we believe that a transmucosal patch is a viable design alternative for fentanyl delivery due to it?s a rapid onset and the potential for diffusive control with the impermeable layer. Further exploration is recommended to evaluate. ItemTreatment of Ocular Alkali Burns Using Extended RinsingLee, Won Young; Ousterout, David; Shin, Mi Ran; Yu, Changhao (2008-07-23T19:18:46Z)Many people work every day around potentially hazardous chemicals that can cause severe burns if the worker is exposed to the substance. Ocular alkali exposure is particularly dangerous and without immediate and proper treatment permanent vision loss will occur. The purpose of this project is to assess the pH levels in the eye, after alkali exposure and during subsequent treatments, by accurately modeling the cornea of the eye. We have found using our model that a typical exposure of 1M NaOH for 20 seconds leads to a pH of 14.1 and 12.7 at corneal surface and stroma/aqueous humor interface. After 15 minutes of rinsing with water, our model predicts pH values of 8.2, 11.8, and 12.0 in the corneal surface, stroma/aqueous humor interface, and aqueous humor, respectively. We have also found that it is vitally important to rinse as quickly as possible after exposure, as our model predicts significantly higher pH values and alkali penetration in the eye after only a few seconds of exposure. We have critically evaluated the sensitivity of this model to input parameters and found that it is relatively sensitive to mass transfer coefficient changes, which drastically reduce the minimum pH at the corneal surface. We also have evaluated our model against published literature to demonstrate its ability to model other given situations, specifically using ionic rinsing solutions instead of water. We believe that this model is accurate for modeling the stroma layer, while there is more work to be done in modeling the aqueous humor, which may have an unknown reaction rate for alkali removal. To obtain a better model of this process, we need to learn more about the physiology of the eye. We conclude that it is critically important that an individual try to use external protective equipment, proper training, and proper technique to prevent any exposure and that in the event of an exposure, rinsing begins immediately so that the chemical does not diffuse as far into the eye thus preventing further damage.